DDB1 E3 ligase controls dietary fructose-induced ChREBPα stabilization and liver steatosis via CRY1.

ABSTRACT: Fructose over-consumption contributes to the development of liver steatosis in part by stimulating ChREBPα-driven de novo lipogenesis. However, the mechanisms by which fructose activates ChREBP pathway remain largely undefined. Here we performed affinity purification of ChREBPα followed by mass spectrometry and identified DDB1 as a novel interaction protein of ChREBPα in the presence of fructose. Depletion and overexpression of Ddb1 showed opposite effects on the ChREBPα stability in hepatocytes. We next tested the impact of hepatic Ddb1 deficiency on the fructose-induced ChREBP pathway. After 3-week high-fructose diet feeding, both Ddb1 liver-specific knockout and AAV-TBG-Cre-injected Ddb1^flox/flox mice showed significantly reduced ChREBPα, lipogenic enzymes, as well as triglyc

SUBMITTER: Tong X 

PROVIDER: S-EPMC7282961 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature